title: Soluble ST2 in ambulatory patients with heart failure: Association with functional capacity and long-term outcomes.
abstract: BACKGROUND
  ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study-a multicenter, randomized study of exercise training in HF.
  
  
  RESULTS
  HF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement.
  
  
  CONCLUSIONS
  ST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, NC.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.forename: Vivian
authors.initials: V
authors.lastname: Thompson
authors.forename: Linda K
authors.initials: LK
authors.lastname: Shaw
authors.forename: Megan L
authors.initials: ML
authors.lastname: Neely
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.forename: Mark P
authors.initials: MP
authors.lastname: Donahue
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.forename: Ileana L
authors.initials: IL
authors.lastname: Piña
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology / Q000534:rehabilitation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D017472:Receptors, Interleukin-1; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1
keywords: biomarkers; heart failure; prognosis